This invention relates to a new and useful process for preparing various carboline derivatives which are of value in the field of chemotherapy. More particularly, it is concerned with a novel process for preparing certain 2-substituted-5-aryl-1,2,3,4-tetrahydro-.gamma.-carboline derivatives, which are known to be useful as tranquilizing agents. The invention also includes the corresponding 2-unsaturated intermediates, which are novel compounds.
In accordance with the prior art, a number of methods have been presented for preparing compounds of this particular type. For instance, in U.S. Pat. No. 4,001,263 to J. J. Plattner et al., there are described several different synthetic routes leading to the compounds of present interest, of which 2-[4-(p-fluorophenyl)-4-hydroxybutyl]-5-(p-fluorophenyl)-8-fluoro-1,2,3,4- tetrahydro-.gamma.-carboline is an especially preferred embodiment. A typical route disclosed therein for preparing the preferred compounds of this particular class involves (1) treating the corresponding 2-unsubstituted-5-aryl-1,2,3,4-tetrahydro-.gamma.-carboline starting material with an appropriate .omega.-haloalkyl nitrile in order to effect alkylation at the 2-position of the molecule, followed by (2) reaction of the resulting nitrile compound with an appropriate aromatic Grignard reagent to yield the desired corresponding ketone and then (3) reduction of the ketone with sodium borohydride to yield the desired final product having the requisite secondary alcohol side chain. However, the aforesaid three-step method suffers from a few disadvantages, viz., the use of expensive reagents and the difficulties normally involved upon handling the Grignard reagent and complex metal hydrides, etc., plus the additional time and expense normally caused by the number of steps involved with the overall process.